Functional MRI of the human nose: an unprecedented investigational window into the nervous system

University Of Minnesota, Minneapolis MN

Investigators

Abstract

ABSTRACT As the major organ responsible for olfaction and air intake, and thanks to its rich connections to the autonomic nervous system, the nose plays many pivotal roles for survival. In fact, disruptions in olfaction and autonomic function are often observed before loss of brain function ensues during the progression of neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. As such, the nose is being increasingly recognized as a critical investigational target for understanding the complex functional interactions between peripheral and central nervous system, identifying mechanisms of action of disease, and even for delivery of therapeutic interventions. Yet, the characterization of system-wide functional connections between the nose and the central nervous system is challenged by the lack of neuroimaging methods which detect robust surrogates of functional activity in the nose. In fact, whereas standard functional MRI techniques are formidable tools for characterizing function in the brain, they are intrinsically inadequate for detecting functional signals in the nose, because the susceptibility artefacts originating from the air-tissue interfaces of the nasal cavity destroy magnetic field uniformity and lead to signal loss with standard fMRI techniques that rely on the use of an echo time (TE). To overcome the challenges of nose fMRI, in this project we will exploit the resilience to susceptibility artefacts offered by ultrashort/zero-TE acquisition schemes, which we previously demonstrated being capable of providing robust fMRI contrast primarily mediated by blood flow. Our pilot data demonstrate that unprecedented fMRI signals during both tasks and resting state can be detected with ultrashort TE (UTE) techniques in the human nasal cavity. Therefore, our plan here is to first optimize these innovative UTE protocols for fMRI of the human nose, and to apply them in cross-sectional and in test-retest studies designed to provide supporting evidence to our overarching hypothesis: UTE enables detection of robust nose fMRI signals primarily mediated by blood flow fluctuations that generally correlate with ANS activity and that during the presentation of odor stimuli specifically reflect olfactory processing in the nose. Protocol optimizations will be first performed to ensure maximum coverage, functional contrast, spatial and temporal resolutions on each of two clinical MRI platforms, 7T and 3T. Detection sensitivity and reproducibility of nose fMRI signals and system-wide connections between nose and the nervous system will be then evaluated on each MRI platform. To determine whether the fMRI nose signals reflect olfactory processing, we will deliver different sensory stimuli (odor, visual and odorless airflow stimuli); to characterize the dependence of nose fMRI signals on the function of the autonomic nervous system, we will correlate the nose fMRI signals with other surrogates of autonomic function such as hearth rate and breathing rate variabilities. Once completed, this study will have demonstrated the first proof-of-principle use of nose fMRI in humans by making use of widely available clinical scanners, thus greatly facilitating translational applications and dissemination to a broad community of researchers and clinicians.